Potassium Bicarbonate Supplementation Lowers Bone Turnover and Calcium Excretion in Older Men and Women: A Randomized Dose-Finding Trial.

The acid load accompanying modern diets may have adverse effects on bone and muscle metabolism. Treatment with alkaline salts of potassium can neutralize the acid load, but the optimal amount of alkali is not established. Our objective was to determine the effectiveness of two doses of potassium bicarbonate (KHCO3 ) compared with placebo on biochemical markers of bone turnover, and calcium and nitrogen (N) excretion. In this double-blind, randomized, placebo-controlled study, 244 men and women age 50 years and older were randomized to placebo or 1 mmol/kg or 1.5 mmol/kg of KHCO3 daily for 3 months; 233 completed the study. The primary outcomes were changes in 24-hour urinary N-telopeptide (NTX) and N; changes in these measures were compared across the treatment groups. Exploratory outcomes included 24-hour urinary calcium excretion, serum amino-terminal propeptide of type I procollagen (P1NP), and muscle strength and function assessments. The median administered doses in the low-dose and high-dose groups were 81 mmol/day and 122 mmol/day, respectively. When compared with placebo, urinary NTX declined significantly in the low-dose group (p = 0.012, after adjustment for baseline NTX, gender, and change in urine creatinine) and serum P1NP declined significantly in the low-dose group (p = 0.004, adjusted for baseline P1NP and gender). Urinary calcium declined significantly in both KHCO3 groups versus placebo (p < 0.001, adjusted for baseline urinary calcium, gender, and changes in urine creatinine and calcium intake). There was no significant effect of either dose of KHCO3 on urinary N excretion or on the physical strength and function measures. KHCO3 has favorable effects on bone turnover and calcium excretion and the lower dose appears to be the more effective dose. Long-term trials to assess the effect of alkali on bone mass and fracture risk are needed.

Dietary fat increases vitamin D-3 absorption.

BACKGROUND: The plasma 25-hydroxyvitamin D response to supplementation with vitamin D varies widely, but vitamin D absorption differences based on diet composition is poorly understood. OBJECTIVES: We tested the hypotheses that absorption of vitamin D-3 is greater when the supplement is taken with a meal containing fat than with a fat-free meal and that absorption is greater when the fat in the meal has a higher monounsaturated-to-polyunsaturated fatty acid ratio (MUFA:PUFA). DESIGN: Open, three-group, single-dose vitamin D-3 comparative absorption experiment. PARTICIPANTS/SETTING: Our 1-day study was conducted in 50 healthy older men and women who were randomly assigned to one of three meal groups: fat-free meal, and a meal with 30% of calories as fat with a low (1:4) and one with a high (4:1) MUFA:PUFA. After a 12-hour fast, all subjects took a single 50,000 IU vitamin D-3 supplement with their test breakfast meal. MAIN OUTCOME MEASURES: Plasma vitamin D-3 was measured by liquid chromatography-mass spectrometry before and 10, 12 (the expected peak), and 14 hours after the dose. STATISTICAL ANALYSES PERFORMED: Means were compared with two-tailed t tests for independent samples. Group differences in vitamin D-3 absorption across the measurement time points were examined by analysis of variance with the repeated measures subcommand of the general linear models procedure. RESULTS: The mean peak (12-hour) plasma vitamin D-3 level after the dose was 32% (95% CI 11% to 52%) greater in subjects consuming fat-containing compared with fat-free meals (P=0.003). Absorption did not differ significantly at any time point in the high and low MUFA and PUFA groups. CONCLUSIONS: The presence of fat in a meal with which a vitamin D-3 supplement is taken significantly enhances absorption of the supplement, but the MUFA:PUFA of the fat in that meal does not influence its absorption.

Effect of supplemental vitamin D and calcium on serum sclerostin levels.

OBJECTIVE: Serum sclerostin levels have been reported to be inversely associated with serum 25OHD levels, but the effect of vitamin D and calcium supplementation on serum sclerostin levels is unknown. This study was carried out to determine whether vitamin D and calcium supplementation altered serum sclerostin levels in healthy older adults. DESIGN: We measured serum sclerostin levels at baseline and after 2 years in 279 men and women who participated in a placebo-controlled vitamin D (700 IU/day) and calcium (500 mg/day) intervention trial carried out in men and women aged ≥65 years. METHOD: Serum sclerostin levels were measured using the MesoScale Discovery chemiluminescence assay. RESULTS: In the men, sclerostin levels increased over 2 years by 4.11±1.81 ng/l (13.1%) in the vitamin D plus calcium-supplemented group and decreased by 3.16±1.78 ng/l (10.9%) in the placebo group (P=0.005 for difference in change). Adjustments for the season of measurement, baseline physical activity levels, baseline serum sclerostin levels, and total body bone mineral content did not substantially alter the changes. In the women, there was no significant group difference in change in serum sclerostin levels either before or after the above-mentioned adjustments. In both the sexes, vitamin D and calcium supplementation significantly increased serum ionized calcium levels and decreased parathyroid hormone levels. CONCLUSION: Men and women appear to have different serum sclerostin responses to vitamin D and calcium supplementation. The reason for this difference remains to be determined.

Serum sclerostin levels vary with season.

CONTEXT: To establish the clinical utility of serum sclerostin levels, it is important to know whether there is seasonal variation in the measurements. OBJECTIVE: This study was done to determine whether serum sclerostin levels vary by season in healthy older men and women. METHODS: Serum sclerostin levels were measured in archived serum of 314 healthy men and women aged 65 years and older and examined for seasonal variation. Several factors known to vary by season and previously reported to be associated with serum sclerostin levels, including serum osteocalcin, physical activity, and serum PTH levels, were also measured in these subjects. Sex did not modify the association of season with sclerostin, so the men and women were analyzed together. RESULTS: Serum sclerostin levels varied significantly by season (P < .001, after adjustment for sex). Sclerostin levels in the wintertime were 20% higher than the all-year mean, the levels gradually declined through the spring and summer, and by the fall, they were 20% below the all-year mean. Adjustment for serum osteocalcin, physical activity, and serum PTH did not alter the seasonal means. Seasonal differences in serum osteocalcin, physical activity, and serum PTH were not statistically significant. CONCLUSIONS: This study documents marked seasonal variation in serum sclerostin levels. It is important to recognize this source of biological variability when considering the potential clinical utility of sclerostin measurements.

Meal conditions affect the absorption of supplemental vitamin D3 but not the plasma 25-hydroxyvitamin D response to supplementation.

It is sometimes assumed that dietary fat is required for vitamin D absorption, although the impact of different amounts of dietary fat on vitamin D absorption is not established. This study was conducted to determine whether the presence of a meal and the fat content of the meal influences vitamin D absorption or the 25-hydroxyvitamin D [25(OH)D] response to supplemental vitamin D3 . Based on earlier studies in rats we postulated that absorption would be greatest in the low-fat meal group. Sixty-two healthy older men and women were randomly assigned to one of three meal groups: no meal, high-fat meal, or low-fat meal; each was given a monthly 50,000 IU vitamin D3 supplement with the test breakfast meal (or after a fast for the no-meal group) and followed for 90 days. Plasma vitamin D3 was measured by liquid chromatography-mass spectroscopy (LC/MS) before and 12 hours after the first dose; plasma 25(OH)D was measured by radioimmunoassay at baseline and after 30 and 90 days. The mean 12-hour increments in vitamin D3 , after adjusting for age and sex, were 200.9 nmol/L in the no-meal group, 207.4 nmol/L in the high-fat meal group, and 241.1 nmol/L in the low-fat meal group (p = 0.038), with the increase in the low-fat group being significantly greater than the increases in the other two groups. However, increments in 25(OH)D levels at 30 and 90 days did not differ significantly in the three groups. We conclude that absorption was increased when a 50,000 IU dose of vitamin D was taken with a low-fat meal, compared with a high-fat meal and no meal, but that the greater absorption did not result in higher plasma 25(OH)D levels in the low-fat meal group.

Treatment with potassium bicarbonate lowers calcium excretion and bone resorption in older men and women.

CONTEXT: Bicarbonate has been implicated in bone health in older subjects on acid-producing diets in short-term studies. OBJECTIVE: The objective of this study was to determine the effects of potassium bicarbonate and its components on changes in bone resorption and calcium excretion over 3 months in older men and women. DESIGN, PARTICIPANTS, AND INTERVENTION: In this double-blind, controlled trial, 171 men and women age 50 and older were randomized to receive placebo or 67.5 mmol/d of potassium bicarbonate, sodium bicarbonate, or potassium chloride for 3 months. All subjects received calcium (600 mg of calcium as triphosphate) and 525 IU of vitamin D(3) daily. MAIN OUTCOME MEASURES: Twenty-four-hour urinary N-telopeptide and calcium were measured at entry and after 3 months. Changes in these measures were compared across treatment groups in the 162 participants included in the analyses. RESULTS: Bicarbonate affected the study outcomes, whereas potassium did not; the two bicarbonate groups and the two no bicarbonate groups were therefore combined. Subjects taking bicarbonate had significant reductions in urinary N-telopeptide and calcium excretion, when compared with subjects taking no bicarbonate (both before and after adjustment for baseline laboratory value, sex, and changes in urinary sodium and potassium; P = 0.001 for both, adjusted). Potassium supplementation did not significantly affect N-telopeptide or calcium excretion. CONCLUSIONS: Bicarbonate, but not potassium, had a favorable effect on bone resorption and calcium excretion. This suggests that increasing the alkali content of the diet may attenuate bone loss in healthy older adults.